P1287: HETROMBOPAG FOR ENHANCEMENT OF PLATELET ENGRAFTMENT IN PATIENTS WITH LYMPHOMA AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: Linjun Zhao, Lingyan Ping, Shaoxuan Hu, Honghong Ding, Xiaopei Wang, Yuqin Song, Jun Zhu, Weiping Liu
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Autologous hematopoietic stem cell transplantation (ASCT) is a common consolidation therapy for patients with lymphoma. Myelosuppression (neutropenia and thrombocytopenia) caused by high-dose conditioning regimens of ASCT may lead to higher mortality. Thus, exploring methods to improve platelet engraftment is very important. Hetrombopag, a novel oral, non-peptide, active small-molecule thrombopoietin-receptor agonist (TPO-RA), can stimulate multiple intracellular signaling pathways (such as JAK/STAT, PI3K/AKT and ERK1/2) by binding to TPO-R. This will promote the proliferation and differentiation of megakaryocytes and platelet production. Previous study suggests that hetrombopag can promote platelet engraftment and decrease platelet transfusion after allogeneic hematopoietic stem cell transplantation. Aims: To evaluate the efficacy and safety of hetrombopag for hematopoietic reconstitution after ASCT in patients with lymphoma. Methods: In this single-arm, phase II trial, patients (18-65 years) with lymphoma who had an Eastern Cooperative Oncology Group performance status 0-1 and normal hematopoietic function (hemoglobin ≥90 g/L) could be enrolled if they were suitable for ASCT. After transplantation, patients received oral hetrombopag 5 mg once daily for 7 consecutive days. Platelet transfusion was allowed if platelet count <10×109/L. The primary endpoint was time to platelet engraftment (the first day of 7 consecutive days with the platelet count ≥20×109/L). Secondary endpoints included time to neutrophil engraftment (the first day of 3 consecutive days with the absolute neutrophil count ≥0.5×109/L), progression-free survival (PFS), overall survival (OS), and safety. Results: Between August 2021 and July 2022, 46 patients were enrolled. The median age was 50.5 (range, 15-64) years and 27 (58.7%) patients were males. Most patients (74%) received ≤6 cycles of induction chemotherapy (median: 6 [range, 2-17] cycles). After hetrombopag treatment, all patients achieved platelet and neutrophil engraftments. The median time to platelet engraftment was 13.5 (range, 10-30) days. The median time to neutrophil engraftment was 11 (range, 9-34) days. All patients received platelet transfusion with a median of 3 (range,1-13) U. As of February 4, 2023, all patients achieved complete response (Lugano 2014 criteria); one (2.2%) patient had relapsed disease and no deaths occurred. The median platelet count (PLT) at 30 days and 50 days after ASCT were 81.5 (range, 22-407) ×109/L and 118 (39-352) ×109/L, and 34 (73.9%) and 45 (97.8%) patients had PLT >50×109/L at 30 days and 50 days, respectively. No secondary failure of platelet recovery occurred. The subgroup analyses indicated that non-Hodgkin lymphoma, BCNU/TT conditioning regimen, and re-infused CD34+ cell counts >5.0×106/kg were associated with faster platelet engraftment (Table 1). Moreover, BCNU/TT conditioning regimen and re-infused CD34+ cell counts >5.0×106/kg were also associated with faster neutrophil engraftment and less platelet transfusion. Of 46 patients, three had diarrhea, two had fever, and one had pulmonary infection. All these adverse events were grade 1-2 and unrelated to hetrombopag. Summary/Conclusion: Hetrombopag shows a well contribution to platelet engraftment and good safety profile in patients with lymphoma undergoing ASCT, which deserves further validations in larger trials.Keywords: Platelet engraftment, Autologous hematopoietic stem cell transplantation